Hemoglobin最新文献

Sickle cell disease (SCD) is a group of inherited disorders characterized by the presence of abnormal hemoglobin S. Patients with SCD suffer from frequent episodes of anemia, chronic hemolysis, pain crisis, and vaso-occlusion. Additionally, SCD is associated with diverse and serious clinical complications, including thrombosis, which can lead to organ failure, increased morbidity, and eventually, mortality. SCD is known to be a hypercoagulable condition, and the cause of hypercoagulability is multifactorial, with the molecular basis of hemoglobin S being the main driver. The presence of hemoglobin S induces sickling of the RBCs and their subsequent hemolysis, as well as oxidative stress. Both of these processes can alter the hemostatic system, through the activation of platelets, coagulation system, and fibrinolysis, as well as depletion of coagulation inhibitors. These changes can also induce the formation of microvesicles and expression of tissue factor, leading to activation of WBCs, endothelial cell damage, and inflammatory response. Understanding the various factors that drive hypercoagulability as a thrombo-inflammatory mechanism in SCD can help provide explanations for the pathogenesis and other complications of the disease.

Hemoglobin (Hb) Hammersmith, formed by serine substitution for phenylalanine at residue 42 in the beta-globin chain, is a very rare variant of unstable hemoglobin with low oxygen affinity. For patients with hemoglobinopathies, it is well-established that hematopoietic stem cell transplantation provides a complete cure, but the literature on its role for those with Hb Hammersmith is limited. A seven-month-old girl who was examined for anemia and splenomegaly was followed up for congenital hemolytic anemia. The patient with visible cyanosis of the lips and whose p50 was low in blood gas was diagnosed with Hb Hammersmith through the DNA sequence analysis. During the follow-up, frequent blood transfusions had to be given due to anemia aggravated by infections. Following a successful hematopoietic stem cell transplant from an HLA-matched sibling, the patient completely recovered from Hb Hammersmith. The case is presented because of its rarity.

We reported the identification of two rare α-thalassemia silent carriers with novel HBA1 mutations of CD 39 -C [Thr > Pro] (HBA1: c.114del; p.Thr39Profs*11) and CD 109 ACC > CCC [Thr > Pro] (HBA1: c.325A > C; p. Thr109Pro), respectively. The two probands were pregnant women diagnosed with mild hypochromic anemia or microcytic hypochromic anemia by routine blood tests. They started iron therapy before taking differential diagnosis from iron deficiency anemia. After wait and watch approach, they both accepted thalassemia genetic screening, which identified CD 39 -C [Thr > Pro] and CD 109 ACC > CCC [Thr > Pro], respectively. Due to inappropriate iron therapy, worse anemia and iron overload were noticed in the first proband, but no obvious side effect was found in both probands. Functional analysis showed that, relative to the wild type, CD 39 -C [Thr > Pro] considerably reduced the expression of the HBA1 protein while CD 109 ACC > CCC [Thr > Pro] only had a minor impact. Our study highlighted the importance of gestational thalassemia screening based on next-generation sequencing for identifying novel rare thalassemia variants and increased our understanding about the relationship between genotype and phenotype of α-thalassemia.

β-Thalassemia is genetic disorder characterized by β-globin chain deficiency resulting from mutations in the β-globin coding gene. Both the quantity and quality of blood produced will be impacted by this condition. The distribution of mutation causing thalassemia is vary across ethnic and different regions in Indonesia. This study aims to identify the variant mutation in patients with β-thalassemia at Tidar Hospital as representative samples of Javanese population, the largest ethnicity in Indonesia. Sixty-one blood samples were obtained from blood transfusion-dependent patients with β-thalassemia. Mutation was identified using ARMS and RFLP PCR-based methods, and inconclusive samples were subjected to DNA sequencing. Results showed that the mutation variants were Cd 26/IVSI-5 (G > C) 47.54%, Cd 26/Cd 35 16.30%, Cd 26/IVSI-1 (G > T) 11.47%, Cd 26/IVSI-2 4.91%, IVSI-5 (G > C)/Cd 40 3.27%; 1.63%; IVSI-5 (G > C)/IVSI-1 (G > A) 1.63%; IVSI-5 (G > C)/Cap + 1 1.63%; Cd 26/Cd 15 1.63%; Cd 26/Cd 30 1.63%. We also found three homozygous of IVSI-1 (G > T), IVSI-5 (G > C) 6.55%, and Cd 35 1.63%. The most prevalent alleles would be recommended to be used as part of screening for β-thalassemia in the Javanese ethnicity in Central Java, especially for families affected by thalassemia.

Growth impairment is a known complication of sickle cell disease (SCD). Few studies explored the potential effects of hydroxyurea (HU) on growth in children with SCD in relation to HU dose and response. This is a prospective study conducted at Sultan Qaboos University Hospital, Oman, and included 91 SCD patients with age below 16 years when started on HU, aiming to explore the potential effect/s of HU on growth parameters of older children with SCD in relation to their clinical improvement and the dose required for this improvement. Weight, height, and body mass index (BMI) were collected at baseline, 6 and 18 months after initiation. Anthropometric data were compared to WHO standards. Initial height and BMI Z scores (HAZ and WAZ) were lower compared to WHO norms. HAZ and WAZ did not change significantly after 6 and 18 months on HU therapy. However, BMI Z-scores improved significantly after 6 and 18 months of follow-up (p value 0.044 and 0.028 respectively). No significant changes were observed in WAZ or HAZ among patients on low dose versus those on high dose. BMI Z score improved significantly after 18 months of low dose group (p = 0.014) but did not change in those on high dose HU. In conclusion, HU therapy did not adversely affect weight and height growth in older children with SCD. BMI Z scores improved at 18 months in patients on low dose but not in those on high dose (p = 0.014).

Hemoglobinopathies are the most common single-gene disorders in humans. There are 1,424 variants of human hemoglobin described with 951 involving the β-globin gene. Ancestry and geography play a significant role in the incidence and nature of hemoglobinopathies, with African, Asian, and Mediterranean populations and their descendants being amongst the most affected. Investigation of variants in individuals of Hispanic descent is needed to reflect the changing demographics of the United States. Hemoglobin β-globin evaluation through gel electrophoresis, high-performance liquid chromatography, and HBB gene sequencing was performed on patients from Texas hospitals between 2010 and 2015 and demographic parameters (age, sex, ethnicity) was subsequently analyzed. A total of 846 patients underwent hemoglobinopathy evaluation. A β chain variant was detected in 628 of the 846 total patients. Hispanic patients represented 37% (314/846 patients), which were equally distributed between females (50%; 156/314) and males (50%; 156/314). A β-globin chain variant was found in 67% of Hispanic patients with a distribution across 10 variants seen in greater than 1% of patients. For hemoglobin variants, an understanding of the regional and ethnic prevalence will improve patient care through more effective screening and identification of the variant, early diagnosis, and appropriate treatment if necessary, and better genetic counseling.

We identified a novel mutation in the SUPT5H gene in a Chinese female who presented with a β-thalassemia trait. The substitution of c.193C > T (p.Arg65*) leads to a premature stop codon on residue 65 and could be associated with haploinsufficiency. This variant was inherited from the mother who also had the asymptomatic phenotype of β-thalassemia trait. Our case further supports the role of SUPT5H as a potential β-globin chain production-modulating gene.

Thalassemia is a major public health concern in India. The thalassemic burden in India is high, with an estimated 100,000 patients diagnosed with β-thalassemia syndrome. However, the exact number is unknown because of the absence of National Registries for patients. India alone contributes to approximately 25% of the global β-thalassemia burden. A possible option to control this burden is to endorse education and awareness programs, compulsory prenatal screening, and develop suitable facilities for genetic counseling, and availability of cost-effective diagnostic tests in India, especially in rural areas. In addition to the various clinical complications associated with thalassemia, lifelong intervention creates mental and physical trauma in patients and their relatives. Government and nongovernment organizations have initiated screening programs to prevent thalassemia. However, prenatal screening is not mandatory, and the reachability of screening programs in rural areas is yet to begin. This review article will discuss the progress in thalassemia research in India, including its prevalence, spectrum of β-thalassemia mutations, preventive and therapeutic measures, and awareness programs. More importantly, we will discuss the need and roadmap to strengthen prevention programs in India.

As the life expectancy in thalassemia is improving, pain is being recognized as an emerging problem. To document the pain prevalence and severity in patients with transfusion-dependent thalassemia all transfusion-dependent thalassemia patients >10 years of age (n = 165) attending the Thalassemia Day Care Center were assessed for pain prevalence, severity, and its effect on various life activities using the Brief Pain Inventory. Their medical records were reviewed for the presence of various co-morbidities. Pain was reported by 62.4% of participants with 35.2% and 59.4% of participants, reporting pain in the past 1 and 4 weeks respectively. A significantly higher pain prevalence was reported in females (p = .037), patients residing in urban areas (p = .038), and employed participants (p = .038). The commonest sites of pain were the lower back and calves. General activity (p = .02) and enjoyment of life (p = .02) were significantly affected due to pain in patients between 21 and 30 years of age. Female participants reported interference of pain with mood (p = .03). A significant correlation of pain prevalence was found with higher average serum ferritin (p = .015), moderate to severe liver iron concentration (p = .04), and lower levels of 25 hydroxyvitamin D levels (p = .03). Pain is an emerging cause of morbidity in thalassemia. The study found a significant association of pain with modifiable factors such as serum ferritin, LIC, and 25 (OH) vitamin D levels.

In this report we decribed a new α-chain variant found during the measurement of hemoglobin A_1c (Hb A_1c) using matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry (MS). MALDI-TOF MS analysis detected an α-chain variant with a mass of 15,155 Da. However, this Hb variant was not detected during Hb A_1c measurement by cation-exchange high-performance liquid chromatography (HPLC) and capillary electrophoresis (CE) methods. Sanger sequencing validated the presence of a heterozygous missense mutation [HBA1: c.239C > T, CD79(GCG > GTG)(Ala > Val)]. The observed 28 Da mass difference exactly matches the theoretical mass difference (28 Da) resulting from the substitution of alanine (89.079) with valine (117.133). As this represents the initial documentation of the mutation, we named it Hb Tangshan after the proband's residence.